The new millennium opens an era of extraordinary, promise for sickle cell disease patients in the United States. Effective therapies are now available and longer, productive lives with proven cost savings are possible; novel treatments are undergoing clinical trials; understanding the biology, of the disease is being energized by new insights into vascular biology and the human genome. To meet the challenges and seize the opportunities of sickle cell disease research, the Boston Sickle Cell Center will carry out novel therapeutic trials in sickle cell anemia and HbSC disease focusing on the induction of HbF and prevention of dehydration of sickle erythrocytes. More basic studies will focus on erythrocyte biology and include studies of cation transport and the effect of hypoxlia and oxidation on the Gardos channel of both normal and sickle erythrocytes and adhesive properties of sickle erythrocytes. The role of nitric oxide in the pathobiology of sickle cell disease will be examined by defining the role of NO in the pulmonary and vascular responses in a sickle cell transgenic mouse. We will also: build a clinical core that will form a foundation for therapeutic trials; provide education and counseling for patients and medical professionals; provide a national resource for hemoglobinopathy testing. All components of the Boston Comprehensive Sickle Cell Center will be melded into a cohesive unit to increase its effectiveness beyond the sum of its components and encourage interactions with other local and national sickle cell centers.